Mendelian susceptibility to mycobacterial diseases (MSMD) is a rare inheritance syndrome, characterized by a disseminated infection with mycobacterium in children following BCG vaccination at birth. Regarding the vaccination program in Iran, it may consider as a public health problem. The pathogenesis of MSMD is dependent on either insufficient production of IFN-gamma (γ) or inadequate response to it. Here, we want to introduce three cases including two siblings and one girl from two unrelated families with severe mycobacterial infections referred to Immunology, Asthma and Allergy Research Institute (IAARI), from 2013 to 2015; their MSMD was confirmed by both cytokine assessment and genetic analysis. Regarding the clinical features of the patients, cell proliferation against a mitogen and BCG antigen was ordered in a lymphocyte transformation test (LTT) setting. ELISA was performed for the measurement of IL-12p70 and IFN- γ in whole blood samples activated by BCG + recombinant human IFN-γ and BCG + recombinant human IL-12, respectively. In contrast to mitogen, the antigen-dependent proliferation activity of the patients' leukocytes was significantly lower than that in normal range. We identified a homozygous mutation in IL12RB1 gene for two kindred who had a homozygous mutation affecting an essential splice site. For the third patient, a novel frameshift deletion in IL12RB1 gene was found. The genetic study results confirmed the impaired function of stimulated lymphocytes to release IFN-γ following stimulation with BCG+IL-12 while the response to rhIFN-γ for IL-12p70 production was relatively intact. Our findings show that cellular and molecular assessments are needed for precise identification of immunodeficiency disorders especially those without clear-cut diagnostic criteria.
Background: Mendelian susceptibility to mycobacterial diseases (MSMD) is a rare inheritance syndrome, characterized by a disseminated infection in children following BCG vaccination performed at their birth time. In the infected children with MSMD, there is a susceptibility to systemic infection with mycobacterium tuberculosis and nontuberculous including Bacillus Calmette-Guerin (BCG) vaccine Aime: We aimed to diagnosis MSMD patients over a period of 2 years at the main referral center for immunological disorders in Iran. Methods & Materials: In this study, suspected patients with MSMD referred to "Immunology, Asthma and Allergy Research Institute" are studied genetically. The patients were affected with localized disseminated and recurrent lymphadenopthy after BCG vaccination at the birth time, and have normal immune system result tests Their LTT function is normal in the exposure with PHA, is defective in the exposure to BCG In this study, we measured Il12, IFN gama levels to help identify patie Results: In this study, we have 4 controls and 8 patients that had impaired response to IL-12. Although there was no significant relationship between LTT with PHA .it becomes signification when we added BCG alive In addition the arrays of IL l12(0.003), IFN gama(0.015) between controls and patient groups was signification Conclusion: Evaluating IFN-g and IL-12 assay can help for quick and short time diagnosis of MSMD disease (defect in IL12r1, receptor1, and defect in IL12 and IFN-g receptor). However genetic investigation in this disease is more complete and definitive for the diagnosis in these patients.
'%3e%3cg id='e'%3e%3cg id='c' fill='none' stroke='%23fff' stroke-width='2'%3e%3cpath id='b' d='M0 1h26M1 10V5h8v4h8V5h-5M4 9h2m20 0h-5V5h8m0-5v9h8V0m-4 0v9' transform='scale(1.4)'/%3e%3cpath id='a' d='M0 7h9m1 0h9' transform='scale(2.8)'/%3e%3cuse xlink:href='%23a' y='120'/%3e%3cuse xlink:href='%23b' y='145.2'/%3e%3c/g%3e%3cg id='d'%3e%3cuse xlink:href='%23c' x='56'/%3e%3cuse xlink:href='%23c' x='112'/%3e%3cuse xlink:href='%23c' x='168'/%3e%3c/g%3e%3c/g%3e%3cuse xlink:href='%23d' x='168'/%3e%3cuse xlink:href='%23e' x='392'/%3e%3c/g%3e%3cg fill='%23da0000' transform='matrix(45 0 0 45 315 180)'%3e%3cg id='f'%3e%3cpath d='M-.548.836A.912.912 0 0 0 .329-.722 1 1 0 0 1-.548.836'/%3e%3cpath d='M.618.661A.764.764 0 0 0 .422-.74 1 1 0 0 1 .618.661M0 1l-.05-1L0-.787a.31.31 0 0 0 .118.099V-.1l-.04.993zM-.02-.85 0-.831a.144.144 0 0 0 .252-.137A.136.136 0 0 1 0-.925'/%3e%3c/g%3e%3cuse xlink:href='%23f' transform='scale(-1 1)'/%3e%3c/g%3e%3c/svg%3e)
'%3e%3cpath fill='%23012169' d='M0 0v30h60V0z'/%3e%3cpath stroke='%23fff' stroke-width='6' d='m0 0 60 30m0-30L0 30'/%3e%3cpath stroke='%23C8102E' stroke-width='4' d='m0 0 60 30m0-30L0 30' clip-path='url(%23b)'/%3e%3cpath stroke='%23fff' stroke-width='10' d='M30 0v30M0 15h60'/%3e%3cpath stroke='%23C8102E' stroke-width='6' d='M30 0v30M0 15h60'/%3e%3c/g%3e%3c/svg%3e)
